ConZip

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Risk of seizures may also increase in patients with
epilepsy, those with a history of seizures, or in patients with a recognized
risk for seizure (such as head trauma, metabolic disorders, alcohol and drug
withdrawal, CNS infections).

In tramadol overdose, naloxone administration may
increase the risk of seizure.

Suicide Risk

Do not prescribe ConZip™ for patients who are suicidal or
addiction-prone. Consideration should be given to the use of non-narcotic
analgesics in patients who are suicidal or depressed [see Drug Abuse And
Dependence].

Prescribe ConZip™ with caution for patients with a
history of misuse and/or are taking CNS-active drugs including tranquilizers or
antidepressant drugs, or alcohol in excess, and patients who suffer from
emotional disturbance or depression [see DRUG INTERACTIONS].

Serotonin Syndrome Risk

The development of a potentially life-threatening
serotonin syndrome may occur with use of tramadol products, including ConZip™,
particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs,
TCAs, MAOIs and triptans, with drugs which impair metabolism of serotonin
(including MAOIs) and with drugs which impair metabolism of tramadol (CYP2D6
and CYP3A4 inhibitors). This may occur within the recommended dose. [see CLINICAL
PHARMACOLOGY].

Anaphylactoid Reactions

Serious and rarely fatal anaphylactoid reactions have
been reported in patients receiving therapy with tramadol. When these events do
occur it is often following the first dose. Other reported allergic reactions
include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis
and Stevens-Johnson syndrome. Patients with a history of anaphylactoid
reactions to codeine and other opioids may be at increased risk and therefore should
not receive ConZip™ [see CONTRAINDICATIONS].

Respiratory Depression

Administer ConZip™ cautiously in patients at risk for
respiratory depression. In these patients alternative non-opioid analgesics
should be considered. If large doses of tramadol are administered with
anesthetic medications or alcohol, respiratory depression may result.
Respiratory depression should be treated as an overdose. If naloxone is to be administered,
use cautiously because it may precipitate seizures [see OVERDOSAGE].

Interaction With Central Nervous System (CNS) Depressants,
Including Alcohol and Drugs of Abuse

Tramadol may be expected to have additive effects when
used in conjunction with alcohol, other opioids, or illicit drugs that cause
central nervous system depression. Use ConZip™ with caution and in reduced
dosages when administered to patients receiving CNS depressants such as
alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers
or sedative hypnotics. ConZip™ increases the risk of CNS and respiratory depression
in these patients. Alcohol-containing beverages should not be consumed by patients
using ConZip™ [see DRUG INTERACTIONS,
and OVERDOSAGE].

Patients with Increased Intracranial Pressure or Head Trauma

Use ConZip™ with caution in patients with increased
intracranial pressure or head injury. The respiratory depressant effects of
opioids include carbon dioxide retention and secondary elevation of
cerebrospinal fluid pressure, and may be markedly exaggerated in these
patients. Additionally, pupillary changes (miosis) from tramadol may obscure
the existence, extent, or course of intracranial pathology. Clinicians should
also maintain a high index of suspicion for adverse drug reaction when
evaluating altered mental status in these patients if they are receiving
ConZip™.

Use in Ambulatory Patients

ConZip™ may impair the mental and or physical abilities
required for the performance of potentially hazardous tasks such as driving a
car or operating machinery. Caution patients initiating therapy with ConZip™ or
those whose dose has been increased to refrain from potentially hazardous
activities until it is established that their mental and physical abilities are
not significantly impaired.

Use With MAO Inhibitors and SSRIs

Use ConZip™ with great caution in patients taking
monoamine oxidase inhibitors. Animal studies have shown increased deaths with
combined administration. Concomitant use of ConZip™ with MAO inhibitors or
SSRI's increases the risk of adverse reactions, including seizure and serotonin
syndrome.

Misuse, Abuse and Diversion of Opioids

ConZip™ contains tramadol, an opioid agonist of the
morphine-type. Such drugs are sought by drug abusers and people with addiction
disorders and are subject to criminal diversion.

Tramadol can be abused in a manner similar to other
opioid agonists, legal or illicit. This should be considered when prescribing
or dispensing ConZip™ in situations where the physician or pharmacist is
concerned about an increased risk of misuse, abuse, or diversion.

ConZip™ could be abused by crushing, chewing, snorting,
or injecting the dissolved product. These practices will result in the
uncontrolled delivery of the opioid and pose a significant risk to the abuser
that could result in overdose and death [see Drug
Abuse And Dependence, and OVERDOSAGE].

Concerns about abuse, addiction, and diversion should not
prevent the proper management of pain. The development of addiction to opioid
analgesics in properly managed patients with pain has been reported to be rare.
However, data are not available to establish the true incidence of addiction in
chronic pain patients. Healthcare professionals should contact their State
Professional Licensing Board, or State Controlled Substances Authority for
information on how to prevent and detect abuse or diversion of this product.

Risk of Overdosage

Serious potential consequences of overdosage with ConZip™
are central nervous system depression, respiratory depression and death. In
treating an overdose, primary attention should be given to maintaining adequate
ventilation along with general supportive treatment [see OVERDOSAGE].

Acute Abdominal Conditions

The administration of ConZip™ may complicate the clinical
assessment of patients with acute abdominal conditions.

Use In Specific Populations

Pregnancy

Teratogenic Effects - Pregnancy Category C

There are no adequate and well-controlled studies in
pregnant women. Use ConZip™ during pregnancy only if the potential benefit
justifies the potential risk to the fetus.

Neonatal seizures, neonatal withdrawal syndrome, fetal
death and still birth have been reported during post-marketing reports with
tramadol HCl immediate-release products. ConZip™ should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus.

Non-teratogenic Effects

Tramadol caused a reduction in neonatal body weight at a
dose of 50 mg/kg (1.6-fold the MDHD) and reduced pup survival at an oral dose of
80 mg/kg (approximately 2.6-fold MDHD) when rats were treated during late
gestation throughout lactation period.

Labor and Delivery

ConZip™ should not be used in pregnant women prior to or
during labor unless the potential benefits outweigh the risks. Safe use in
pregnancy has not been established. Chronic use during pregnancy may lead to
physical dependence and post-partum withdrawal symptoms in the newborn [see Drug
Abuse And Dependence]. Tramadol has been shown to cross the placenta. The
mean ratio of serum tramadol in the umbilical veins compared to maternal veins
was 0.83 for 40 women given tramadol during labor.

The effect of ConZip™, if any, on the later growth,
development, and functional maturation of the child is unknown.

Nursing Mothers

ConZip™ is not recommended for obstetrical preoperative
medication or for postdelivery analgesia in nursing mothers because its safety
in infants and newborns has not been studied. Following a single IV 100 mg dose
of tramadol, the cumulative excretion in breast milk within 16 hours post-dose
was 100 μg of tramadol (0.1% of the maternal dose) and 27 μg of M1.
It is not known whether this drug is excreted in human milk following an oral
dose.

Pediatric Use

The safety and efficacy of ConZip™ in patients under 18
years of age have not been established. The use of ConZip™ in the pediatric
population is not recommended.

Geriatric Use

In general, caution should be used when selecting the
dose for an elderly patient. Usually, dose administration should start at the
low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal or cardiac function and of concomitant disease or other drug
therapy.

Eight hundred and twelve elderly (65 years of age or
older) subjects were exposed to ConZip™ in clinical trials. Of those subjects,
two hundred and forty were 75 years of age and older. In general, higher
incidence rates of adverse events were observed for patients older than 65
years of age compared with patients 65 years and younger, particularly for the
following adverse events: nausea, constipation, somnolence, dizziness, dry
mouth, vomiting, asthenia, pruritus, anorexia sweating, fatigue, weakness,
postural hypotension and dyspepsia. For this reason, ConZip™ should be used with
great caution in patients older than 75 years of age [see DOSAGE AND
ADMINISTRATION].

Patients with Renal Impairment

ConZip™ has not been studied in patients with renal
impairment. Impaired renal function results in a decreased rate and extent of
excretion of tramadol and its active metabolite, M1. The limited availability
of dose strengths of ConZip™ does not permit the dosing flexibility required
for safe use in patients with severe renal impairment. Therefore, ConZip™
should not be used in patients with severe renal impairment [see DOSAGE AND ADMINISTRATION,
WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Patients with Hepatic Impairment

ConZip™ has not been studied in patients with hepatic
impairment. The limited availability of dose strengths of ConZip™ does not
permit the dosing flexibility required for safe use in patients with severe
hepatic impairment. Therefore, ConZip™ should not be used in patients with
severe hepatic impairment [see DOSAGE AND ADMINISTRATION, WARNINGS
AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.